DESCRIPTION: The ability of melatonin to prolong life is controversial and debatable. The evidence to support life prolongation are based on 1) serum melatonin falls progressively with age, 2) melatonin may be important in aging by virtue of its antioxidant and enhancement of immune function, and 3) two limited studies suggest that melatonin extends mean survival. A key goal of this application is to confirm or refute the initial observations and extend these findings in a laboratory having expertise in aging, antioxidant studies and immune functions. The three aims of this proposal are to determine if melatonin: 1) Prolongs life span and delays age related pathologies, 2) Reduces free radical generation, 3) Enhances immune competence. Male Fischer 344 rats will be given two doses (4 and 16 (g/ml) of melatonin. Controls will include ad libitum and calorically restricted animals (the most effective anti-aging method). Analysis will include mean life span as well as the delay of age-related pathologies. In separate studies, the effect of melatonin on oxidative stress and immune function will be examined. Together, these studies will indicate whether melatonin has broad anti-aging effects, including actions on antioxidant activity and immune function.